An investigation on the evolution of granule formation by in-process sampling of a high shear granulator

Understanding the growth mechanisms in granulation process is an important topic, providing valuable insights and supports control strategies. Typically, observations in high shear granulators are made after stopping the process. In this work, an in-process sampling technique is described and applied to a high shear wet granulation process. Different samples can be collected over the cause of the high shear granulation process. This allowed observation of the evolution of granules during addition of water at a constant flowrate. For a typical pharmaceutical formulation, we observed that granules nucleate in the first 2 minutes after water addition starts and then grows in size and strength to an average size of 200–1200 μm at 12.5 minutes, corresponding to a sharp increase in torque. Longer water addition times lead to oversized granules and eventually a paste and highly fluctuating torque. Sampling was continued after stopping water addition which showed with time larger formed granules smoothen, whilst the smaller weaker ones disintegrate. The work shows the in-process sampling can facilitate the identification of the required binder quantity in high shear granulation.